Compounds of formula ##STR2## wherein R.sub.1 is hydrogen or a lower alkyl radical and n is 4, 5, or 6 are known in U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. The uses disclosed are: protective effect against cramp induced by thiosemicarbazide; protective action against cardiazole cramp; the cerebral diseases, epilepsy, faintness attacks, hypokinesia, and cranial traumas; and improvement in cerebral functions. The compounds are useful in geriatric patients. The patents are hereby incorporated by reference.
U.S. Pat. No. 5,270,317 and its divisional U.S. Pat. No. 5,352,788 disclose compounds of formula ##STR3## in which: R.sub.1 and R.sub.2 are similar or different and are each independently hydrogen or a group selected from a C.sub.1 -C.sub.6 alkyl, a C.sub.1 -C.sub.4 alkoxy, an amino, an aminomethyl, a carboxyl, an alkoxycarbonyl in which the alkoxy is C.sub.1 -C.sub.4, a cyano, a tetrazolyl, a methyltetrazolyl, a methylsulfonylamino, a trifluoromethylsulfonylamino, a trifluoromethylsulfonylaminomethyl, an N-cyanoacetamide, an N-hydroxyacetamide, an N-(4-carboxy-1,3-thiazol-2-yl)acetamide, a ureido, a 2-cyanoguanidinocarbonyl, a 2-cyanoguanidinomethyl, an imidazol-1-yl-carbonyl, and a 3-cyano-2-methylisothioureidomethyl, with the proviso that at least one of the substituents R.sub.1 or R.sub.2 is other than hydrogen;
R.sub.3 is a hydrogen, a C.sub.1 -C.sub.6 alkyl which is unsubstituted or substituted by one or more halogen atoms, a C.sub.2 -C.sub.6 alkenyl, a C.sub.3 -C.sub.7 cycloalkyl, a phenyl, a phenylalkyl in which the alkyl is C.sub.1 -C.sub.3, or a phenylalkenyl in which the alkenyl is C.sub.2 -C.sub.3, said phenyl groups being unsubstituted, or monosubstituted or polysubstituted by a halogen atom, a C.sub.1 -C.sub.4 alkyl, a C.sub.1 -C.sub.4 halogenoalkyl, a C.sub.1 -C.sub.4 polyhalogenoalkyl, a hydroxyl, or a C.sub.1 -C.sub.4 alkoxy; and either PA1 R.sub.4 and R.sub.5 are each independently a C.sub.1 -C.sub.6 alkyl, a phenyl or a phenylalkyl in which the alkyl is C.sub.1 -C.sub.3, said alkyl, phenyl, and phenylalkyl groups being unsubstituted or substituted by one or more halogen atoms or by a group selected from a C.sub.1 -C.sub.4 perfluoroalkyl, a hydroxyl, and a C.sub.1 -C.sub.4 alkoxy; PA1 or R.sub.4 and R.sub.5 together form a group of the formula .dbd.CR.sub.7 R.sub.8, in which R.sub.7 is hydrogen, a C.sub.1 -C.sub.4 alkyl or a phenyl, and R.sub.8 is a C.sub.1 -C.sub.4 alkyl or a phenyl: PA1 or else R.sub.4 and R.sub.5 together are either a group of the formula (CH.sub.2).sub.n or a group of the formula (CH.sub.2).sub.p Y--(CH.sub.2).sub.q, in which Y is either an oxygen atom, or a sulfur atom, or a carbon atom substituted by a C.sub.1 -C.sub.4 alkyl group, a phenyl or a phenylalkyl in which the alkyl is C.sub.1 -C.sub.3, or a group N--R.sub.6, in which R.sub.6 is a hydrogen, a C.sub.1 -C.sub.4 alkyl, a phenylalkyl in which the alkyl is C.sub.1 -C.sub.3, a C.sub.1 -C.sub.4 alkylcarbonyl, a C.sub.1 -C.sub.4 alkylcarbonyl, a C.sub.1 -C.sub.4 halogenoalkylcarbonyl, a C.sub.1 -C.sub.4 polyhalogeno-alkylcarbonyl, a benzoyl, an alphaaminoacyl or an N-protecting group, or R.sub.4 and R.sub.5, together with the carbon atom to which they are bonded, form an indane or an adamantane; PA1 p+q=m; PA1 n is an integer between 2 and 11; and PA1 m is an integer between 2 and 5; or PA1 R.sub.4 is a C.sub.1 -C.sub.6 alkyl which is unsubstituted or substituted by one or more halogen atoms; and PA1 R.sub.5 is a cycloalkyl or a cycloalkylmethyl, said cycloalkyl being C.sub.3 -C.sub.7, which is unsubstituted or substituted by one or more halogen atoms: PA1 or R.sub.4 and R.sub.5 are each a cyclopropyl; PA1 X is an oxygen atom or sulfur atom; and PA1 z and t are zero or one is zero and the other is one; and their salts. PA1 R is hydrogen or lower alkyl. PA1 (ii) NaCN, EtOH/H.sub.2 O, PA1 (iii) EtOH, HCl PA1 (iv) H.sub.2 O/H.sup.+, PA1 (v) H.sub.2, Rh/C, MeOH, PA1 (vi) HCl PA1 (iii) Raney nickel, EtOH/H.sub.2 O, PA1 (iv) HCl PA1 (ii) H.sub.2 SO.sub.4 ; PA1 (iii) Ac.sub.2 O; PA1 (iv) MeOH; PA1 (v) Curtius Reaction; PA1 (vi) HCl, H.sub.2 O then anion exchange PA1 (iii) Ac.sub.2 O; PA1 (iv) H.sub.2 NOH; PA1 (v) PhSO.sub.2 Cl; PA1 (vi) Et.sub.3 N, MeOH; PA1 (vii) HCl, H.sub.2 O then anion exchange PA1 (ii) NaCN, EtOH/H.sub.2 O; PA1 (iii) BnOH, HCl; PA1 (iv) H.sub.2 O/H.sup.+ ; PA1 (v) H.sub.2, Rh/C, MeOH PA1 (iii) SnCl.sub.2, HCl/H.sub.2 O
The compounds are disclosed as having the ability to antagonize angiotension II.
J. Med. Chem., 38:3772-3779 (1995) covers the syntheses of spiropiperidines as potent and selective non-peptide tackykinin NK.sub.2 receptor antagonists.